We propose to study the role and effect of augmented zinc in biological systems in vitro and in vivo on various immunologically related reactions: mechanisms of immune sensitization, immune effector mechanisms and the target organ - the renal allograft. Based on our previous observations, zinc acts to affect various reactive cells: macrophages, polymorphonuclear leucocytes, lymphocytes, and platelets. These cell types in various combinations and states of reactivity are involved in the primary and the secondary immune response. The effect of zinc on these immune responses as well as cell mediated cytoxic reactions will be evaluated. The classical and alternate pathways of the complement system are involved in many immunological reactions. Prior work in our laboratory has indicated that increased but nontoxic levels of zinc exerts a profound effect on the complement system. The present proposal will investigate the mechanisms whereby zinc acts on in vitro complement involved reactions: alternate pathway activation, complement dependent PMN lysosomal release and platelet release and aggregation reactions. The complement dependent in vivo inflammation reactions (Arthus and Forssman reactions) will be studied to determine if zinc can modify their severity. The already proven protective effect of zinc to stabilize cell membranes will be applied to preventing ischemic injury to stored donor renal allografts. As a final goal of this proposal, the application of zinc to the canine renal allograft model in efforts to determine how zinc can modify the entire immunological capability of the animal in a manner that allows better organ functional survival will be studied. These studies will be carried out using a wide range of immunological techniques - in vitro and in vivo, to study the effects of zinc on specific aspects of complex immunological reactions. This proposal is a continuation of the work done on the existing NIH Grant AM 16489 which expires 9/30/75.